Zhi Qi

Find an error

Name:

Organization: Xiamen University

Department:

Title:

Chemicals
References

Structure–activity relationship of Baifuzi-cerebrosides on BKCa channel activation

Co-reporter:Li Zhou, Yu-Jiao Zhang, Li-Juan Gao, Ying Ye, Jian-Hua Qi, Zhi Qi

European Journal of Medicinal Chemistry 2014 Volume 75() pp:301-307

Publication Date(Web):21 March 2014

DOI:10.1016/j.ejmech.2014.01.007

•We isolated 5 cerebrosides from Baifuzi and determined their chemical structures.•Four cerebrosides significantly activated the BK channel.•Acyl chain lengths of the cerebrosides potently affect the channel activation.•Double bond configuration of the cerebrosides weakly affected the channel.Our previous study reported that a mixture of cerebrosides from traditional Chinese medicine Baifuzi could activate BKCa channel. It is curious to know the effect of each single cerebroside on the channel. Here we isolated 5 pure cerebrosides from the mixture and determined their chemical structures. The most potent one increased the single channel open probability 6 folds with EC50 value of 1.0 μM. The structure–activity relationship revealed that acyl chain length of cerebrosides has potent effect, while configuration of double bond at C8–C9 on their long chain base has weak effect on the channel activity. Thus, this research provides a guide for design and synthesis of a lead cerebroside with more potent effect on the BKCa channel.The longer the acyl chain length, the more efficient the cerebrosides to activate the BKCa channel.

Hypericin prolongs action potential duration in hippocampal neurons by acting on K+ channels

Co-reporter:Y Wang;X Shi;Z Qi

British Journal of Pharmacology 2010 Volume 159( Issue 7) pp:1402-1407

Publication Date(Web):

DOI:10.1111/j.1476-5381.2009.00513.x

Background and purpose: Synaptic deficiency is generally accepted to be involved in major depression, and accordingly classic antidepressants exert their effects through enhancing synaptic efficiency. Hypericin is one of the major active constituents of extracts of St. John's Wort (Hypericum perforatum L.) with antidepressive actions, but little is known about its therapeutic mechanisms. Our aim was to explore whether hypericin has a modulatory effect on neuronal action potential (AP) duration by acting on voltage-gated ion channels.

Experimental approach: We used voltage-clamp and current-clamp techniques in a whole-cell configuration to study primary cultures of neonatal rat hippocampal neurones. We measured the effects of extracellularly applied hypericin on AP duration as well as on voltage-gated Na⁺, I_A and I_K currents.

Key results: Extracellularly applied hypericin dose-dependently increased AP duration but barely affected its amplitude. Further analysis revealed that hypericin inhibited both transient I_A and delayed rectifier I_K potassium currents. In contrast, hypericin exerted no significant effect on both Na⁺ peak current and its decay kinetics.

Conclusions and implications: Extracellularly applied hypericin increased AP duration, which might be ascribed to its effect on I_A and I_K currents. As a small increase in AP duration could lead to a dramatic increase in synaptic efficiency, our results imply that hypericin might exert its antidepressant effects by enhancing presynaptic efficiency.

Baifuzi reduces transient ischemic brain damage through an interaction with the STREX domain of BKCa channels

Co-reporter:S Chi, W Cai, P Liu, Z Zhang, X Chen, L Gao, J Qi, L Bi, L Chen and Z Qi

Cell Death & Disease 2010 1(1) pp:e13

Publication Date(Web):2010-01-01

DOI:10.1038/cddis.2009.10

Stroke is a long-term disability and one of the leading causes of death. However, no successful therapeutic intervention is available for the majority of stroke patients. In this study, we explored a traditional Chinese medicine Baifuzi (Typhonium giganteum Engl.). We show, at first, that the ethanol extract of Baifuzi exerts neuroprotective effects against brain damage induced by transient global or focal cerebral ischemia in rats and mice. Second, the extract activated large-conductance Ca2+-activated K+ channel (BKCa) channels, and BKCa channel blockade suppressed the neuroprotection of the extract, suggesting that the BKCa is the molecular target of Baifuzi. Third, Baifuzi cerebroside (Baifuzi-CB), purified from its ethanol extract, activated BKCa channels in a manner similar to that of the extract. Fourth, the stress axis hormone-regulated exon (STREX) domain of the BKCa channel directly interacted with Baifuzi-CB, and its deletion suppressed channel activation by Baifuzi-CB. These results indicate that Baifuzi-CB activated the BKCa channel through its direct interaction with the STREX domain of the channel and suggests that Baifuzi-CB merits exploration as a potential therapeutic agent for treating brain ischemia.